Regulation of Circadian Behavior by Astroglial MicroRNAs in Drosophila

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

article

Samantha You¹  Tudor A. Fulga²  David Van Vactor²  F. Rob Jackson¹ 

[1] Department of Neuroscience, Sackler Program in Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts 02111;Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115

关键词: glial biology;    astrocyte;    circadian behavior;    microRNA;   

DOI  :  10.1534/genetics.117.300342

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

We describe a genome-wide microRNA (miRNA)-based screen to identify brain glial cell functions required for circadian behavior. To identify glial miRNAs that regulate circadian rhythmicity, we employed a collection of “miR-sponges” to inhibit miRNA function in a glia-specific manner. Our initial screen identified 20 glial miRNAs that regulate circadian behavior. We studied two miRNAs, miR-263b and miR-274, in detail and found that both function in adult astrocytes to regulate behavior. Astrocyte-specific inhibition of miR-263b or miR-274 in adults acutely impairs circadian locomotor activity rhythms with no effect on glial or clock neuronal cell viability. To identify potential RNA targets of miR-263b and miR-274, we screened 35 predicted miRNA targets, employing RNA interference-based approaches. Glial knockdown of two putative miR-274 targets, CG4328 and MESK2, resulted in significantly decreased rhythmicity. Homology of the miR-274 targets to mammalian counterparts suggests mechanisms that might be relevant for the glial regulation of rhythmicity.

【 授权许可】

CC BY